Abstract Background A progressive rise in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a prognostic marker of disease progression and is associated with an increased risk of mortality in patients with transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM). Acoramidis, a selective TTR stabilizer providing near-complete (≥90%) TTR stabilization, has recently been approved in Europe and the USA for the treatment of patients with ATTR-CM. In the phase 3 ATTRibute-CM study, acoramidis reduced cardiovascular death and cardiovascular-related hospitalization, and blunted the progressive rise in NT-proBNP, compared with placebo. Purpose To assess the effect of acoramidis on the improvement in NT-proBNP at Month 30 (M30) compared with baseline (BL) in participants with ATTR-CM from the phase 3 ATTRibute-CM study. Methods Randomized participants in ATTRibute-CM received acoramidis or placebo (2:1). Three analyses of NT-proBNP were performed in the modified intention-to-treat population (N=611). The first analysis evaluated the proportion of participants with a net decrease in NT-proBNP at M30, relative to BL. The other two analyses assessed the change from BL at M30 in NT-proBNP by disease progression category in all participants (imputed analysis; participants with missing NT-proBNP assessment at BL or M30 categorized as worsened) and in participants with assessments available at both BL and M30 (observed analysis). NT-proBNP disease progression categories were: clinically meaningful improvement (decrease 300 ng/L and 30% from BL); clinically meaningful worsening (increase 300 ng/L and 30% from BL); and stability (change in NT-proBNP at M30 not meeting disease improvement or worsening criteria). Results Overall, 611 participants (acoramidis: 409; placebo: 202) were analysed; BL characteristics were comparable. Median (interquartile range) NT-proBNP at BL was similar in the acoramidis (2273 1315, 3872 ng/L) and placebo (2274 1128, 3590 ng/L) groups. At M30, almost half (45%) of the participants receiving acoramidis experienced a net decrease in NT-proBNP (any decrease from BL) compared with 9% of participants receiving placebo (Figure). In the imputed analysis, at M30, a greater proportion of acoramidis recipients (49.9%) experienced improved or stable NT-proBNP levels than placebo recipients (17.3%; Table). In participants who survived until M30 and had assessments available (observed analysis), improved/stable disease was observed in 72.9% and 26.3% of participants receiving acoramidis and placebo, respectively (Table). Conclusions Acoramidis treatment resulted in improved or stable NT-proBNP at M30 in about 50% of study participants compared with fewer than 20% with placebo, indicating a clinically meaningful improvement in NT-proBNP and better stabilization of their disease. Further studies are warranted to assess the durability of these effects and implications for the long-term clinical benefits of acoramidis.
Sarswat et al. (Sat,) studied this question.